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Metabolic mechanisms underlying the heterogeneity of major adverse cardiovascular (CV) event (MACE) risk in individuals with type 2 diabetes mellitus (T2D) remain unclear. We hypothesized that circulating metabolites reflecting mitochondrial dysfunction predict incident MACE in T2D. Targeted mass-spectrometry profiling of 60 metabolites was performed on baseline plasma samples from the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS; discovery cohort) and Exenatide Study of Cardiovascular Event Lowering (EXSCEL; validation cohort) biomarker substudy cohorts. A principal components analysis metabolite factor comprising medium-chain acylcarnitines (MCACs) was associated with MACE in TECOS and validated in EXSCEL, with higher levels associated with higher MACE risk. Meta-analysis showed that long-chain acylcarnitines (LCACs) and dicarboxylacylcarnitines were also associated with MACE. Metabolites remained associated with MACE in multivariate models and favorably changed with exenatide therapy. A third cohort (Cardiac Catheterization Genetics [CATHGEN]) with T2D was assessed to determine whether these metabolites improved discriminative capability of multivariate models for MACE. Nine metabolites (MCACs and LCACs and 1 dicarboxylacylcarnitine) were associated with time to MACE in the CATHGEN cohort. Addition of these metabolites to clinical models minimally improved the discriminative capability for MACE but did significantly down reclassify risk. Thus, metabolites reporting on dysregulated mitochondrial fatty acid oxidation are present in higher levels in individuals with T2D who experience subsequent MACE. These biomarkers may improve CV risk prediction models, be therapy responsive, and highlight emerging risk mechanisms.

Background: Although appropriate noninvasive cardiac tests (NICTs) after an acute coronary syndrome (ACS) provide useful prognostic information, inappropriate use leads to inefficient expenditure of existing healthcare resources. By using the Alberta Contemporary Acute Coronary Syndrome Patient Invasive Treatment Strategies (COAPT) Registry, we evaluated the use and costs of NICTs among patients discharged within 1 year after ACS. Methods: All patients discharged from the hospital with a primary diagnosis of ACS in Alberta between 2004/2005 and 2015/2016 were included. Frequency of NICTs (stress tests [± imaging] and nonstress imaging tests) was determined from linked provincial databases. Costs were obtained from the Alberta Health Care Insurance Plan Medical Procedure List. Results: Of 55,516 patients with ACS, 30,760 had at least 1 NICT (55.4%), with 13,505 (24.3%) having > 1 NICT performed within 1 year. Temporal trends of NICT increased over time (stress tests: P trend < 0.001; nonstress imaging tests: P trend < 0.001). NICT most commonly occurred within the first 4 months after hospital discharge (stress tests at 2 months; nonstress imaging tests at 3-4 months). In 2015/2016, the total estimated costs of NICT were $1.35M, a 22.4% increase from 2004/2005 (1.10M) (P < 0.001), whereas a decrease in incidence of ACS over the same time period was noted (P = 0.008). Conclusions: Rates of NICT 1 year after ACS are high and increasing over time. Estimated costs of NICT appear to be escalating out of proportion to the ACS growth. Further investigation is warranted because it is speculative whether the increase in NICT and costs results in clinical benefit after ACS. Résumé: Contexte: Bien que les différents examens cardiaques non effractifs (ECNE) effectués après un syndrome coronarien aigu (SCA) fournissent des renseignements utiles au pronostic, leur emploi dans des situations inappropriées entraîne un gaspillage des ressources en santé. À l’aide du registre COAPT (Contemporary Acute Coronary Syndrome Patient Invasive Treatment Strategies) de l’Alberta, nous avons évalué l’emploi des ECNE et les coûts qui y sont associés chez les patients qui ont reçu leur congé de l’hôpital dans l’année suivant un SCA. Méthodologie: Tous les patients qui ont reçu leur congé de l’hôpital après un diagnostic primaire de SCA en Alberta entre 2004-2005 et 2015-2016 ont été inclus. La fréquence des ECNE (épreuves d’effort [avec ou sans examen d’imagerie] et examens d’imagerie au repos) a été déterminée à partir des bases de données provinciales couplées. Les coûts ont été établis à partir de la liste des actes médicaux du régime d’assurance-maladie de l’Alberta. Résultats: Des 55 516 patients ayant présenté un SCA, 30 760 ont subi au moins un ECNE (55,4 %) dans l’année qui a suivi l’événement; 13 505 (24,3 %) d’entre eux ont subi plus d’un ECNE. Les tendances temporelles en matière d’ECNE affichent une hausse (épreuves d’effort : p tendance < 0,001; examens d’imagerie au repos : p tendance < 0,001). Les ECNE ont généralement été effectués au cours des 4 premiers mois après la sortie de l’hôpital (épreuves d’effort, dans les 2 mois; examens d’imagerie au repos, dans les 3 à 4 mois). Le coût total des ECNE effectués en 2015-2016 a été évalué à 1,35 M$, soit une hausse de 22,4 % par rapport à 2004-2005 (1,10 M$) (p < 0,001), tandis que l’incidence des SCA a diminué au cours de la même période (p = 0,008). Conclusions: Les taux d’ECNE effectués dans l’année suivant un SCA sont élevés et augmentent au fil du temps. Le coût estimatif de ces ECNE semble s’accroître de façon disproportionnée par rapport à la croissance des SCA. Une enquête plus approfondie s’impose; à l’heure actuelle, on ne peut que spéculer quant aux bienfaits cliniques qui découlent de l’augmentation des ECNE effectués après un SCA et des coûts qu’ils engendrent.

Background There are limited data to inform policy mandating primary percutaneous coronary intervention (PPCI) volume benchmarks for catheterization laboratories in low‐ and middle‐income countries. Methods and Results This prospective state‐wide registry included ST‐segment–elevation myocardial infarction patients with symptoms of

Background Postoperative clinical outcomes associated with the preoperative continuation or discontinuation of angiotensin‐converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) before cardiac surgery remain unclear. Methods and Results In a single‐center, open‐label, randomized, registry‐based clinical trial, patients undergoing nonemergent cardiac surgery were assigned to ACEI/ARB continuation or discontinuation 2 days before surgery. Among the 584 patients screened, 261 met study criteria and 126 (48.3%) patients were enrolled. In total,121 patients (96% adherence; 60 to continuation and 61 to ACEI/ARB discontinuation) underwent surgery and completed the study protocol, and follow‐up was 100% complete. Postoperative intravenous vasopressor use (78.3% versus 75.4%, P=0.703), vasodilator use (71.7% versus 80.3%, P=0.265), vasoplegic shock (31.7% versus 27.9%, P=0.648), median duration of vasopressor (10 versus 5 hours, P=0.494), and vasodilator requirements (10 versus 9 hours, P=0.469) were not significantly different between the continuation and discontinuation arms. No differences were observed in the incidence of acute kidney injury (1.7% versus 1.6%, P=0.991), stroke (no events, mortality (1.7% versus 1.6%, P=0.991), median duration of mechanical ventilation (6 versus 6 hours, P=0.680), and median intensive care unit length of stay (43 versus 27 hours, P=0.420) between the treatment arms. Conclusions A randomized study evaluating the routine continuation or discontinuation of ACEIs or ARBs before cardiac surgery was feasible, and treatment assignment was not associated with differences in postoperative physiological or clinical outcomes. These preliminary findings suggest that preoperative ACEI/ARB management strategies did not affect the postoperative course of patients undergoing cardiac surgery. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT02096406.

BackgroundThe effectiveness of radial access (RA) in ST‐elevation myocardial infarction (STEMI) has been predominantly established in primary percutaneous coronary intervention (pPCI) with limited exploration of this issue in the early postfibrinolytic patient. The purpose of this study was to compare the effectiveness and safety of RA versus femoral (FA) access in STEMI undergoing either a pharmacoinvasive (PI) strategy or pPCI. Methods and ResultsWithin STrategic Reperfusion Early After Myocardial Infarction (STREAM), we evaluated the relationship between arterial access site and primary outcome (30‐day composite of death, shock, congestive heart failure, or reinfarction) and major bleeding according to the treatment strategy received. A total of 1820 STEMI patients were included: 895 PI (49.2%; rescue PCI [n=379; 42.3%], scheduled PCI [n=516; 57.7%]) and 925 pPCI (50.8%). Irrespective of treatment strategy, there was comparable utilization of either access site (FA: PI 53.4% and pPCI 57.6%). FA STEMI patients were younger, had lower presenting systolic blood pressure, lesser Thrombolysis In Myocardial Infarction risk, and more ∑ST‐elevation at baseline. The primary composite endpoint occurred in 8.9% RA versus 15.7% FA patients (P

Background Whether prehospital point‐of‐care (POC) troponin further accelerates the time to diagnosis in patients with chest pain (CP) is unknown. We conducted a randomized trial of POC‐Troponin testing in the ambulance. Methods and Results Patients with chest pain presenting by ambulance were randomized to usual care (UC) or POC‐Troponin; ST‐elevation myocardial infarction patients or those with noncardiovascular symptoms were excluded. Pre‐hospital high‐sensitivity troponin was analyzed on a POC device and available to the paramedic and emergency department (ED) staff. The final diagnosis was centrally adjudicated. The primary endpoint was time from first medical contact to discharge from ED or admission to hospital. We randomized 601 patients in 19 months; 296 to UC and 305 to POC‐Troponin. After ambulance arrival, the first troponin was available in 38 minutes in POC‐Troponin and 139 minutes in UC. In POC‐Troponin, the troponin was >0.01 ng/mL in 17.4% and >0.03 ng/mL in 9.8%. Patients spent a median of 9.0 hours from first medical contact to final disposition, and 165 (27.4%) were admitted to the hospital. The primary endpoint was shorter in patients randomized to POC‐Troponin (median 8.8 hours [6.2–10.8] compared to UC (median 9.1 hours [6.7–11.2]; P=0.05). There was no difference in the secondary endpoint of repeat ED visits, hospitalizations, or death in the next 30 days. Conclusions In this broad population of patients with CP, ambulance POC‐Troponin accelerated the time to final disposition. Enhanced and more cost‐effective early ED discharge of the majority of patients with CP calling 911 is an unrealized opportunity. Clinical Trial Registration URL: https://www.ClinicalTrials.gov/. Unique identifier: NCT01634425.